Photobiomodulation inhibits inflammation in the temporomandibular joint of rats.

Photobiomodulation (PBM) has been applied as a non-invasive technique for treating temporomandibular joint symptoms, especially on painful condition's relief, however the anti-inflammatory mechanism underlying the effect of PBM remains uncertain. This study aims to evaluate the mechanisms of action of PBM (808 nm) in a carrageenan-induced inflammation on temporomandibular joint (TMJ) of rats. In this study male Wistar rats were pre-treated with irradiation of a low-power diode laser for 15 s on TMJ (infra-red 808 nm, 100 mW, 50 J/cm2 and 1.5 J) 15 min prior an injection in the temporomandibular joint of carrageenan (100 µg/TMJ). 1 h after the TMJ treatments, the rats were terminally anesthetized for joint cavity wash and periarticular tissues collect. Samples analysis demonstrated that PBM inhibit leukocytes chemotaxis in the TMJ and significantly reduces amounts of TNF-α, IL-1ß and CINC-1. In addition, Western blotting analysis demonstrated that PBM significantly decreased the protein levels of P2X3 and P2X7 receptors in the periarticular tissues. On the other hand, PBM was able to increase protein level of IL-10 (anti-inflammatory cytokine). In summary, it is possible to suggest that PBM inhibit inflammatory chemotaxis, modulation the balance of the pro- and anti-inflammatory characteristics of inflammatory cells.

Notch Regulates Fibrocartilage Stem Cell Fate and Is Upregulated in Inflammatory TMJ Arthritis.

The Notch pathway is critical for the development of the extracellular matrix in cartilage by regulating both anabolic and catabolic cellular activities. Similarly, Notch signaling plays a biphasic role in adult cartilage health and osteoarthritis by maintaining homeostasis and contributing to degeneration, respectively. The temporomandibular joint (TMJ) is the synovial joint of the craniofacial complex and is subject to injury and osteoarthritis. While Notch has been studied in axial skeletal joints, little is known about the role of Notch in TMJ development and disease. We identified fibrocartilage stem cells (FCSCs) localized within the TMJ condyle superficial zone niche that regenerate cartilage and repair joint injury. Here we investigate the role of Notch in regulating TMJ development and FCSC fate. Using a Notch reporter mouse, we discovered FCSCs localized within the TMJ superficial niche exhibit Notch activity during TMJ morphogenesis. We further showed that constitutively activating Notch promotes FCSC differentiation toward both cartilage and bone lineages, but inhibits adipogenesis. Using a TNF-α-induced TMJ inflammatory arthritis mouse model, we found that the expression of Notch receptors and ligands are upregulated and coupled with cells undergoing cartilage to bone transdifferentiation, which may contribute to TMJ pathogenesis. We also discovered that global Notch inhibition reduces osteogenic and chondrogenic differentiation of FCSCs. Together, these findings suggest that Notch is critical for FCSC fate specification and TMJ homeostasis, and reveal that inhibition of the Notch pathway may be a new therapeutic target for treating TMJ osteoarthritis.

Propargylglycine decreases neuro-immune interaction inducing pain response in temporomandibular joint inflammation model.

The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1ß in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.

Mechanisms involved in antinociception induced by a polysulfated fraction from seaweed Gracilaria cornea in the temporomandibular joint of rats.

Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K+ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K+ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by µ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K+ATP channel pathway, besides of HO-1.

Hedgehog signal expression in articular cartilage of rat temporomandibular joint and association with adjuvant-induced osteoarthritis.

OBJECTIVE: The aim of this study was to investigate the changes in hedgehog (Hh) expression and its possible effects on cartilage degeneration in adjuvant-induced temporomandibular joint osteoarthritis (TMJOA) of rats. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into experimental osteoarthritis (OA) and sham control groups. The bilateral TMJs of six rats from each group were harvested at three, seven, 14, and 28 days. Histological changes in condylar cartilage were assessed by hematoxylin and eosin, toluidine blue, and safranin O staining. The expression of Hh signal-related proteins including Indian hedgehog (Ihh), patched-1 (Ptch1), smoothened (Smo), glioma-associated oncogene homologue1 (Gli1) in cartilage was assessed by immunohistochemistry and Western blot. The protein expression of matrix metalloproteinase-13 (MMP-13), type X collagen, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) in cartilage was evaluated by Western blot. RESULTS: The histological analysis showed marked cartilage degeneration in adjuvant-induced OA groups, including reduced cartilage cellular density, thinner and degraded cartilage, and decreased proteoglycan content in the extracellular matrix. Compared with matched control groups, the expression of Ihh, Ptch1, Smo, and Gli1 in the OA groups was higher in a time-dependent manner. The protein levels of MMP-13, type X collagen, and ADAMTS-5 were substantially increased in OA cartilage compared with those in matched control rats. CONCLUSION: These results indicate that the activation of Ihh signaling may be correlated with pathological changes of condylar cartilage in adjuvant-induced TMJOA.

Effects of cranberry components on IL-1ß-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

OBJECTIVE: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1ß (IL-1ß) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1ß-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DESIGN: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1ß (0.001-1nM)±NDM (25-250µg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. DATA ANALYSIS: ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: NDM did not affect cell viability but inhibited IL-1ß stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-κB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1ß+NDM. CONCLUSION: Cranberry NDM inhibition of IL-1ß-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.

Investigation of an autologous blood treatment strategy for temporomandibular joint hypermobility in a pig model.

Many different surgical and non-surgical techniques are used for the treatment of temporomandibular joint (TMJ) hypermobility. One of these methods is autologous blood injection into the TMJ. The fate of the autologous blood used for treatment of recurring condylar dislocation is still not completely understood. The authors used 12 pigs (Sus scrota f. domestica) as a model species for autologous blood delivery into the TMJ. Blood injection was followed by histopathological analysis at different times after treatment (1h, 1, 2 and 4 weeks). Samples were examined by magnetic resonance imaging, macroscopic and histological methods. The deposition of the remaining blood was observed in the form of clots in the distal parts of the upper joint cavity 1h and 1 week after treatment. 2 weeks after treatment, small blood clots were still apparent in the distal part of the upper joint cavity. 4 weeks after surgery, no remnants of blood, changes or adhesions were apparent inside the TMJ. No morphological or histological changes were observed in the TMJ after the injection of autologous blood suggesting another mechanism is involved in the hypermobility treatment.

Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

BACKGROUND: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). METHODS: The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. RESULTS: Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. CONCLUSIONS: Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system.

Antinociceptive and anti-inflammatory effects of electroacupuncture on experimental arthritis of the rat temporomandibular joint.

This study investigated the antinociceptive and anti-inflammatory effects of electroacupuncture (EA) on zymosan-induced acute arthritis of the rat temporomandibular joint (TMJ). Male Wistar rats were injected with saline or zymosan (control group; 2 mg) into the left TMJ. Low frequency EA (10 Hz, 30 min) was performed at acupoints (LI4, LI11, ST36, ST44) or sham points 2 h after or 1 h before zymosan administration. Mechanical hypernociception was accessed by the electronic Von Frey method after zymosan administration. Rats were sacrificed 6 h after zymosan administration and the joint was removed for histopathological analysis, myeloperoxidase activity assessment, vascular permeability observations, and immunohistochemical verification of inflammatory mediators. The results showed that EA inhibited zymosan-induced hypernociception, compared with the control group and with the sham group (p < 0.05). The results showed that EA inhibited inflammatory parameters such as neutrophil migration, vascular permeability, and tumour necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in the TMJ compared with the sham group (p < 0.05). Histopathological analysis showed that EA significantly inhibited edema and periarticular infiltration (p < 0.05) compared with the control and sham groups. EA at acupoints produced antinociceptive and anti-inflammatory effects on zymosan-induced arthritis in the rat TMJ.

Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction.

Females report temporomandibular joint (TMJ) pain more than men and studies suggest estrogen modulates this pain response. Our goal in this study was to determine genes that are modulated by physiological levels of 17ß-estradiol that could have a role in TMJ pain. To complete this goal, saline or complete Freund's adjuvant was injected in the TMJ when plasma 17ß-estradiol was low or when it was at a high proestrus level. TMJ, trigeminal ganglion, and trigeminal subnucleus caudalis/upper cervical cord junction (Vc/C(1-2) ) tissues were isolated from the treated rats and expression of 184 genes was quantitated in each tissue using real-time PCR. Significant changes in the amount of specific transcripts were observed in the TMJ tissues, trigeminal ganglia, and Vc/C(1-2) region when comparing rats with high and low estrogen. GABA A receptor subunit α6 (Gabra6) and the glycine receptor α2 (Glra2) were two genes of interest because of their direct function in neuronal activity and a >29-fold increase in the trigeminal ganglia was observed in proestrus rats with TMJ inflammation. Immunohistochemical studies showed that Gabrα6 and Glrα2 neuronal and not glial expression increased when comparing rats with high and low estrogen. Estrogen receptors α and ß are present in neurons of the trigeminal ganglia, whereby 17ß-estradiol can alter expression of Gabrα6 and Glrα2. Also, estrogen receptor α (ERα) but not ERß was observed in satellite glial cells of the trigeminal ganglia. These results demonstrate that genes associated with neurogenic inflammation or neuronal excitability were altered by changes in the concentration of 17ß-estradiol.

Ectopic ACTH syndrome associated with large-cell neuroendocrine carcinoma of the lung.

Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well-known paraneoplastic phenomenon, an association with large-cell neuroendocrine carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He did not have a typical Cushingoid appearance nor used diuretics. His newly noted hypertension, hypokalemia (plasma potassium (K) concentration 1.8 mEq/L) with renal K wasting, and metabolic alkalosis suggested a state of mineralocorticoid excess. His plasma renin activity and aldosterone concentrations were low, but cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His hypokalemia and hypertension were controlled with spironolactone and K supplementation. This is the first reported case of EAS in LCNEC and should be kept in mind as a cause of hypokalemia in lung cancer patients.

Tumor necrosis factor-alpha in temporomandibular joint synovial fluid predicts treatment effects on pain by intra-articular glucocorticoid treatment.

The aim of this study was to investigate the influence of tumor necrosis factor-alpha (TNF-alpha) in temporomandibular joint (TMJ) synovial fluid and blood on the treatment effect on TMJ pain by intra-articular injection of glucocorticoid in patients with chronic inflammatory TMJ disorders. High pretreatment level of TNF-alpha in the synovial fluid was associated with a decrease of TNF-alpha and elimination of pain upon maximal mouth opening. Elimination of this TMJ pain was accordingly associated with decrease in synovial fluid level of TNF-alpha. There was also a significant decrease of C-reactive protein and TMJ resting pain after treatment. In conclusion, this study indicates that presence of TNF-alpha in the synovial fluid predicts a treatment effect of intra-articular injection of glucocorticoid on TMJ movement pain in patients with chronic TMJ inflammatory disorders.

Nerve terminals extend into the temporomandibular joint of adjuvant arthritic rats.

The innervation of the temporomandibular joint (TMJ) has attracted particular interest because of the close association with complex mandibular movement. Although the pathological changes of disk innervation may have a crucial role in the development of TMJ pain, the innervation of the TMJ disk by experimentally induced arthritis has rarely been examined in detail. Arthritic rats were induced by injection with 0.1ml solution of Complete Freund's adjuvant (CFA). We investigated three-dimensional distribution of nerve fibers in the TMJ disk using immunohistochemistry for protein gene product-9.5 (PGP-9.5) and calcitonin gene-related peptide (CGRP) in naive and arthritic rats. To clarify the possible role of nerve growth factor (NGF) and its receptor on changes in peripheral innervation of the TMJ, the expressions of trkA and p75 receptor in trigeminal ganglia were examined. Although PGP-9.5 and CGRP immunoreactive (ir) fibers were seen in the peripheral part of the TMJ disk, they were not seen in its central part. The total length and the length density of PGP-9.5 ir and CGRP ir nerve fibers increased in arthritic rats. The innervation area of fibers proliferating in the rostro-medial part merged with that of fibers in the rostro-lateral part in the arthritic rats. In addition, the ratio of trkA- and p75-positive small- and medium-sized cells increased in trigeminal ganglia. It is assumed that increasing innervation of the TMJ disk may be important for the pathophysiology of TMJ pain. NGF and its receptors are likely involved in pathological changes of the TMJ disk.

Attenuation of pro-inflammatory neuropeptide levels produced by a cyclooxygenase-2 inhibitor in an animal model of chronic temporomandibular joint inflammation.

AIMS: To study the neurogenic effects of a cyclooxygenase-2 (COX-2) inhibitor, rofecoxib, in an animal model of persistent inflammation. METHODS: Arthritis was induced within the temporomandibular joint (TMJ) by placing complete Freund's adjuvant (CFA) within the superior joint space of the TMJ in adult male rats. The CFA animals were divided into 2 groups, with 1 group given the COX-2 inhibitor, rofecoxib, on days 21 through 28. Tissues were taken from experimental and control animals 4 weeks post-injection and analyzed by radioimmunoassay. The inflammatory-related neuropeptide, immunoreactive calcitonin gene-related peptide (CGRPi), was assayed from both the TMJ tissues and the trigeminal brain stem subnucleus caudalis. RESULTS: CGRPi content was significantly increased in TMJ tissues within the untreated CFA group (72%) and was found to be effectively no different between the CFA/COX-2 group and controls. Trigeminal brain stem subnucleus caudalis CGRPi levels were not different between the groups. CONCLUSION: These results suggest that use of an inhibitor selective for the inducible form of cyclooxygenase enzyme, COX-2, may significantly attenuate the neurogenic component in an inflammatory TMJ animal model.

PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, whose activation has been linked to several physiologic pathways including those related to the regulation of insulin sensitivity. Here, we investigate effects of PPARgamma specific ligands, rosiglitazone and pioglitazone, on formation of nitrotyrosine and increased expression of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and intercellular adhesion molecule-1 (ICAM-1) in adjuvant-induced murine arthritis. Administration of rosiglitazone or pioglitazone (30 mg/kg, p.o.) significantly inhibited the adjuvant-induced increase in formation of nitrotyrosine and expression of iNOS on both ankle and temporomandibular joints. Rosiglitazone also inhibited the adjuvant-induced expression of M30 positive cells, as a marker of apoptosis, in the joint tissues. In addition, treatment with rosiglitazone or pioglitazone (30 microM) inhibited lipopolysaccharide plus tumor necrosis factor (TNF)-alpha-induced protein expression of iNOS, cyclooxygenase-2, ICAM-1 and nitrotyrosine formation in RAW 264 cells, a murine macrophage-like cell line. Rosiglitazone or pioglitazone inhibited increase in phosphorylated I-kappaB (pI-kappaB) expression, as an index of activation of nuclear factor (NF)-kappaB, in both joint tissues and RAW264 cells. Furthermore, in PPARgamma-transfected HEK293 cells, rosiglitazone inhibited the TNF-alpha-stimulated response using NF-kappaB-mediated transcription reporter assay. These results indicate that PPARgamma ligands may possess anti-inflammatory activity against adjuvant-induced arthritis via the inhibition of NF-kappaB pathway.

Central mu opioid receptor mechanisms modulate mustard oil-evoked jaw muscle activity.

The injection of the small-fibre excitant and inflammatory irritant mustard oil (MO) into the temporomandibular joint (TMJ) region of rats evokes a sustained and reversible increase in electromyographic (EMG) activity of jaw muscles. The 'rekindling' of this nociceptive reflex by intrathecal (i.t.) administration of the opiate antagonist naloxone and mu but not delta and kappa selective opioid antagonist, suggests that it may be modulated by endogenous opioid inhibitory mechanisms.

Collagen I and II mRNA distribution in the rat temporomandibular joint region during growth.

The distribution of type I and II collagen synthesis in the temporomandibular joint (TMJ) area of 1- to 28-day-old rats was studied after hybridization with probes to pro alpha1(I) and pro alpha1(II) collagen mRNA, and stain intensity through the various cartilaginous zones of the mandibular condyle and other areas of TMJ was assessed. The pro alpha(I) collagen mRNA was detected in the perichondrium/periosteum, in the fibrous and undifferentiated cell layers of the mandibular condyle, in the articular disc, and in all bone structures and muscles. The pro alpha1(II) collagen mRNA was found in the condylar cartilage and the articular fossa. Intensity in the condyle was highest in the chondroblastic layer and decreased towards the lower hypertrophic layer. In the condylar cartilage of the 21- to 28-day-old rats the chondroblastic cell zone was relatively narrow compared with the younger animals, whereas the reverse seems to be the case in the cartilage of the articular fossa. Changes in the pro alpha1(II) collagen mRNA were observed in the osseochondral junction area of the primary spongiosa, in that at the age of 5 days intense staining was found, whereas no staining was observed by 14 days. In the mineralizing zone, however, the majority of osteoblastic cells gave a positive signal with the pro alpha1(I) collagen probe. In conclusion, type II collagen synthesis of the mandibular condyle is restricted to its upper area. This differs from the long bone epiphyseal plate, where this type of collagen is produced virtually throughout the cartilage. Type II collagen synthesis of the fossal cartilage seems to increase as a function of age.

Synovial fluid sampling from the temporomandibular joint: sample quality criteria and levels of interleukin-1 beta and serotonin.

The aims of this study were to compare two sets of quality criteria (SQC A and B) with respect to synovial fluid (SF) sampling and to present temporomandibular joint (TMJ) SF levels of IL-1 beta and 5-HT. The study comprised 310 TMJ SF samples from 12 healthy individuals (HI) and 59 patients with TMJ inflammatory disorders. Ten HI and 37 patients were selected for investigation of TMJ SF levels and samples were obtained by a push-and-pull method with quantification by vitamin B12. The SQC comprised aspirate weight (AW), dilution factor (DF), blood contamination and hemolysis. IL-1 beta and 5-HT levels did not differ between the samples that satisfied SQC A or B. The proportion of samples that satisfied SQC A was higher than for SQC B. Patients with polyarthritides had significantly higher TMJ SF concentrations of 5-HT and IL-1 beta than HL. In conclusion, there is a recovery of TMJ SF of 0.1-0.2 g with the method used and the criteria set with the highest success rate do not differ from the other one with respect to SF levels of IL-1 beta and 5-HT. This set of sample quality criteria comprised no hemolysis, no or only minor blood contamination, AW > 0.5 g and DF < 0.98. The higher SF levels in the diseased TMJ (polyarthritides) compared to the healthy joint with respect to 5-HT and IL-1 beta is of clinical diagnostic relevance and the presence of 5-HT or IL-1 beta in TMJ SF seems to indicate a pathological joint condition probably of an inflammatory nature.

Interleukin-1beta in synovial fluid from the arthritic temporomandibular joint and its relation to pain, mobility, and anterior open bite.

PURPOSE: The purpose of this study was to investigate whether interleukin-1beta in synovial fluid or blood plasma is involved in the development of pain or hyperalgesia of the temporomandibular joint (TMJ), as well as reduced mandibular mobility and anterior open bite. PATIENTS AND METHODS: Twenty-nine patients with TMJ arthritis and seven healthy subjects were studied. VAS measurement of TMJ tenderness on palpation of the TMJ (TDP), TMJ pressure pain threshold and tolerance level (PPTL), mandibular mobility, pain during joint movements, and degree of anterior open bite (AOB) were assessed. IL-1beta levels were analyzed in TMJ synovial fluid (SF-IL-1beta) and blood samples and correlated with the preceding factors. RESULTS: SF-IL-1beta showed significant positive correlations with VAS measurement of pain, TDP, and AOB and a negative correlation with PPTL. CONCLUSIONS: This study indicates that IL-1beta in the synovial fluid is associated with pain and hyperalgesia in the TMJ region as well as an anterior open bite. Concerning the latter condition, IL-1beta seems to be a warning signal of tissue destruction.